The regulation of myometrial contractility and uterine responsiveness during pregnancy can be considered in different phases.'For much of pregnancy (phase 0) the myometrium is in a state of relative quiescence. It is acted upon by inhibitors that may include progesterone, prostacyclin, relaxin, parathyroid hormone-related peptide, and nitric oxide. It is evident that withdrawal of the action of one or more of these compounds from the myometrium may occur in relation to labor at term. It is also apparent that premature withdrawal of one or more of these compounds from the myometrium could predispose to premature delivery. Uterine contractility at term can be considered in two stages: activation (phase 1) and stimulation (phase 2). During activation the myometrium is influenced by uterotrophins, among which estrogen is presumed to have a dominant role. Estrogen increases the expression of contraction-associated proteins (CAPS). These include connexin-43, the major protein comprising gap junctions between myocytes during labor, receptors for oxytocin and prostaglandins, and changes leading to increased functional activity of ion channels. With activation, the uterus can then be stimulated by the action of uterotonins, among which oxytocin and prostaglandins are believed to have a predominant role (see ref. 2).

In this chapter, we consider the role of prostaglandins in parturition. At the outset it is meaningful to ask two critical questions: First, are prostaglandins initiators of parturition? Clearly, the answer is no. The initiation of parturition can be considered at the latest during the switch from quiescence to activation (phase 0 to phase l), and probably much earlier. Second, are prostaglandins obligatory for parturition? Again, the answer is likely no. Lessons from experiments with gene null mutations and transgenesis in a variety of systems have indicated the existence of backup and alternative processes. Prostaglandin synthase type I1 (PGHS-11) knock-out mice have reduced fertility and have not been studied in relation to gestation length.'Prostaglandin synthase type I knock-out mice may have protracted labor, and do deliver, although the young have poor viability! The best indications for an im-